Cited by 129Barrier Structure and Function StudiesCholesterol and Lipid MetabolismCaveolin-1 and cellular processes

SR-BI Mediated Transcytosis of HDL in Brain Microvascular Endothelial Cells Is Independent of Caveolin, Clathrin, and PDZK1

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Fung, Karen Y., Wang, Changsen, Nyegaard, Steffen, Heit, Bryan, Fairn, Gregory D., Lee, Warren L.·2017·Frontiers in Physiology

Abstract

The vascular endothelium supplying the brain exhibits very low paracellular and transcellular permeability and is a major constituent of the blood-brain barrier. High-density lipoprotein (HDL) crosses the blood-brain barrier by transcytosis, but technical limitations have made it difficult to elucidate its regulation. Using a combination of spinning-disc confocal and total internal reflection fluorescence microscopy, we examined the uptake and transcytosis of HDL by human primary brain microvascular endothelial cell monolayers. Using these approaches, we report that HDL internalization requires dynamin but not clathrin heavy chain and that its internalization and transcytosis are saturable. Internalized HDL partially co-localized with the scavenger receptor BI (SR-BI) and knockdown of SR-BI significantly attenuated HDL internalization. However, we observed that the adaptor protein PDZK1-which is critical to HDL-SR-BI signaling in other tissues-is not required for HDL uptake in these cells. Additionally, while these cells express caveolin, the abundance of caveolae in this tissue is negligible and we find that SR-BI and caveolin do not co-fractionate. Furthermore, direct silencing of caveolin-1 had no impact on the uptake of HDL. Finally, inhibition of endothelial nitric oxide synthase increased HDL internalization while increasing nitric oxide levels had no impact. Together, these data indicate that SR-BI-mediated transcytosis in brain microvascular endothelial cells is distinct from uptake and signaling pathways described for this receptor in other cell types.

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Crossref · 10.3389/fphys.2017.00841

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  • Cholesterol does not cross from the periphery into the central nervous system, and small HDL particles possibly traverse by endocytosis to a small extent.

    “Cholesterol does not cross from the periphery into the central nervous system (CNS) and small HDL particles possibly traverse by endocytosis to a small extent [15].”

    From Sterol and lipid analyses identifies hypolipidemia and apolipoprotein disorders in autism associated with adaptive functioning deficits (2021) · cites this paper as [15]

    The Introduction (page unavailable) says HDL can cross the blood–brain barrier by transcytosis, which involves endothelial internalization, and the Conclusion reports HDL moving from the apical to the basolateral surface in a cell model. The paper does not specify that the particles are small or that only a small amount crosses. It also does not establish the categorical claim that peripheral cholesterol cannot enter the CNS. (LLM, conf=0.86)

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Authors
Fung, K. Y., Wang, C., Nyegaard, S., Heit, B., Fairn, G. D., & Lee, W. L.
Affiliations
  • St. Michael's Hospital (CA)
  • Hospital for Sick Children (CA)
  • Western University (CA)
Corresponding author
  • Fairn, Gregory D.
  • Lee, Warren L.
Venue
Frontiers in Physiology
Published
2017-10-30
Volume
8
Pages
841-841
ISSN
1664-042X (ISSN-L)
OpenAlex
W2766769123
Cited by
129
References
46
Citations by year
2026: 7 · 2025: 17 · 2024: 13 · 2023: 13 · 2022: 17 · 2021: 20 · 2020: 18 · 2019: 16 · 2018: 8
FWCI
5.66
Type
journal article
Language
en
Open access
Licence
cc-by
Locations
  • Frontiers in Physiology (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
  • Heart and Stroke Foundation of Canada
  • Natural Sciences and Engineering Research Council of Canada
Topics
  • Life Sciences › Neuroscience › Neurology › Barrier Structure and Function Studies
  • Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Caveolin-1 and cellular processes
Keywords
scavenger receptor BI, brain microvascular endothelial cells, blood-brain barrier, caveolin-1, caveolae, clathrin, dynamin, PDZK1, endothelial nitric oxide synthase, nitric oxide, lipoprotein uptake

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